Adherens junctions are multiprotein complexes that mediate cellular adhesion and cell-cell communication.. Signaling mediated through cadherins, the transmembrane components of adherens junctions, at sites of cell-cell contact generates cellular responses, such as changes in gene expression and cytoskeletal rearrangements. Alterations in expression or function of cadherins and other functional proteins have been associated with the metastasis of many types of epithelial carcinomas. Therefore, delineation of signal transduction pathways regulated in response to cadherin-based cell adhesion could provide insights into the molecular mechanisms associated with the progression of cancer. The overall goal of this investigation is to study cadherin-based cell adhesion and the processes it regulates using the model system Drosophila melanogaster. Recent studies indicate that the Drosophila protein Armadillo, a key component of the adherens junctions that links cadherins to the actin cytoskeleton, interacts functionally with the non-receptor tyrosine kinase Abelson and its substrate, Enabled, during cell-cell adhesion of epithelial cells. Therefore, genetic and biochemical experiments will be used to analyze the relationship of Armadillo with Abelson and Enabled for cell adhesion during development. Furthermore, microarray analysis will be used to identify target genes regulated in response to cadherin-based adhesion. Identification of even a single target gene will aid m the characterization of pathways that transduce signals from cadherins to the nucleus.